CORE D - ABSTRACT The UCSF ADRC Neuropathology, Biospecimens, and Genetics core (NP core, Core D) provides vital research support to the UCSF ADRC and to the neurodegenerative disease research community at UCSF and beyond. Neurodegenerative disease pathology and genetics have become increasingly exciting and complex in recent years, with major advances arising from work accomplished through this ADRC. In this renewal application, the NP Core will continue to be led by Dr. William Seeley. Dr. Lea Grinberg will found a new Biospecimens sub-core, and Drs. Dan Geschwind and Giovanni Coppola will continue to lead the Genetics sub-core at UCLA. The NP Core aims to: (1) Obtain and bank human biomaterial for neuropathological, biochemical, and genetic charaterization; (2) Analyze specimens and document results, including NP diagnoses rendered using current diagnostic consensus criteria, and (3) Enter NP, bioassay, and genetics results into research-oriented databases and distribute specimens. These core functions will support the aims of Projects 1 (EOAD variants), 2 (PPA heterogeneity), and 3 (iPSC models) by providing final neuropathological diagnoses, organizing and conducting biochemical analyses, and providing genotyping and gene expression analysis. Moreover, the NP Core will help to further develop a unique bank of specially handled materials (brain, spinal cord, CSF, plasma, urine, RNA/DNA) for ongoing and future molecular, translational, clinicopathological, and biomarker discovery research.